Topical Glucocorticoids with Increased Benefit/Risk Ratio. Current Problems in Dermatology. Vol. 21. Series Editor G. Burg, Zurich
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1 Topical Glucocorticoids with Increased Benefit/Risk Ratio Current Problems in Dermatology Vol. 21 Series Editor G. Burg, Zurich KARGER Basel Freiburg Paris London New York New Delhi Bangkok Singapore Tokyo Sydney Topical Glucocorticoids with Increased Benefit/Risk Ratio Volume Editors H.C. Korting, Munich H.I. Maibach, San Francisco, Calif. 58 figures, 10 color plates, 47 tables, 1993 KARGER Basel Freiburg Paris London New York New Delhi Bangkok Singapore Tokyo Sydney Current Problems in Dermatology Library of Congress Cataloging-in-Publication Data Topical glucocorticoids with inaeased benefit/risk ratio volume editors, H.C. Korting, H.I. Maibach. (Current problems in dermatology; vol. 21) Includes bibliographical references and index, (alk. paper) 1. Glucocorticoids - Therapeutic use. 2. Transdermal medication.3. Dermatopharmacology. I. Korting, Hans Christian. II. Maibach, Howard I. III. Series. [DNLM: 1. Glucocorticoids, Topical. 2. Odds Ratio Wl CU804LV /QV60T ] RM292.3.T '.364-dc20 ISBN Drug Dosage. The authors and the publisher have exerted every effort to ensure that drag selection and dosage set forth in this text are in accord with current recommendations and practice at the time of
2 publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drag reactions, the reader is urged to check the package insert for each drag for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 1993 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland) Printed in Switzerland on acid-free paper by Thür AG Offsetdruck, Pratteln ISBN Contents Preface VII Principal Considerations Do We Need New and Different Glucocorticoids? A Re-Appraisal of the Various Congeners and Potential Alternatives 1 Smith, E.W. (Grahamstown) Design of Novel Soft Corticosteroids 11 Bodor, N. (Gainesville, Fla.) Basic Pharmacologic Considerations Glucocorticoid Receptors 20 Ponec, M. (Leiden) Methods of Computer-Aided Drug Design and Their Applications to Steroids 29 Stouch, T.R. (Princeton, N.J.) Percutaneous Absorption of Topical Corticosteroids 45 Wester, R.C.; Maibach, H.I. (San Francisco, Calif) Metabolism of Topical Drugs within the Skin, in Particular Glucocorticoids 61 Kubota, K.; Ademola, J.; Maibach, H.I. (San Francisco, Calif) Influence of Glucocorticoids on the Epidermal Langerhans Cell 67 Mommaas, A.M. (Leiden) Effect of Glucocorticosteroids on Number and Function of Connective-Tissue Cells 73
3 Hein, R. (Regensburg) Topical Tretinoin Prevents Corticosteroid-induced Atrophy without Lessening the Anti-Inflammatory Effect 79 Kligman, L.H. (Philadelphia, Pa.); Schwartz, E. (New York, N.Y.); Lesnik, R.H. (Philadelphia, Pa.); Mezick, J.A. (Raritan, N.J.) Applied Pharmacologic Considerations Ranking of Topical Glucocorticoids. Principles and Results 89 Smith, E.W.; Haigh, J.M. (Grahamstown) Suppression of Induced Inflammation in Man 97 Kerscher, M.J. (Munich) The Psoriasis Plaque Test and Topical Glucocorticoids: Evaluation by Computerized Laser Profilometry 107 Wolff, H.H.; Kreusch, J.F.; Wilhelm, K.-P.; Klaus, S. (Lübeck) Topical Glucocorticoids and Thinning of Normal Skin as to Be Assessed by Ultrasound 114 Korting, H.C. (Munich) Side Effects of Topical Glucocorticoids 122 Mills, CM.; Marks, R. (Cardiff) Early Detection of Glucocorticoid-Specific Epidermal Alterations Using Skin Surface Microscopy 132 Schulz, H. (Bergkamen); Nietsch, K.H.; Höhler, Th. (Frankfurt/Main) Influence of Glucocorticoid Substances and the Vehicle on Skin Irritancy: Determination by Profilometry 140 Korting, H.C. (Munich) Prednicarbate after Different Forms of Administration. Plasma Levels of Drug and Metabolites and Effects on Endogenous Cortisol Levels in Humans 147 Barth, J. (Bochum); Hochhaus, G.; Derendorf, H. (Gainesville, Fla.); Lehr, K.H.; Höhler, Th. (Frankfurt/Main); Moelimann, H. (Bochum) Clinical Considerations Clinical Efficacy of Topical Glucocorticoid Preparations and Other Types of Dermatics in Inflammatory Diseases, Particularly in Atopic Dermatitis 157 Niedner, R.; Schöpf, E. (Freiburg i.br.) Contact Allergy to Topical Glucocorticoids 170 Eisner, P. (Zurich) Adverse Drug Reactions to Various Topical Glucocorticosteroids: Quantitative Aspects 180 Höhler, Th.; Wörz, K.; Himmler, V. (Frankfurt/Main) Topical Glucocorticoids and Anti-lnfectives: A Rational Combination? 186 Zienicke, H. (Munich)
4 Future Prospects Topical Glucocorticoids: What Has Been Achieved? What Is Still to Be Done? 192 Schafer-Korting, M. (Frankfurt/Main) Subject Index 203 Contents VI Preface The introduction of a topical glucocorticoid, i.e., hydrocortisone, into the treatment of inflammatory skin disease by Sulzberger and Witten in 1952 provided a major pharmacologic breakthrough. In fact, we distinguish two eras of dermatologie treatment, i.e., before and after 'cortisone'. However, it was clear early that hydrocortisone and hydrocortisone acetate alone would not suffice as adequate treatment for all types of inflammatory skin disease. Fortunately, other glucocorticoids such as fluorinated congeners offered additional potency. Yet as early as in 1964, Epstein et al. described 'atrophic striae' due to the apphcation of triamcinolone acetonide; many other local adverse effects have subsequently been documented. Even more potent glucocorticoids, e.g., clobetasol propionate, gave us still more efficacy. However, this was linked to more and more severe adverse effects both of the local and the systemic type. For decades topical glucocorticoids represent the class of topical dermatics most often used, and, in fact, it is not mainly hydrocortisone that is prescribed in daily practice but the more potent congeners. Thus it does not come as a surprise that today the typical adverse effects due to topical glucocorticoids are well known to patients. In fact, some are so scared that the term 'corticophobia' has been proposed. An exaggerated fear of topical glucocorticoids in general, however, can have severe consequences if, for example, severe atopic eczema which can lead to growth retardation is not adequately treated in childhood. In recent years it has been a challenge both to the chemists and the dermatologists to develop glucocorticoids which are potent but to at least a lesser extent linked to systemic and/or local unwanted effects. Several years ago, prednicarbate became available, and since the early days of its clinical application, some dermatologists shared the belief that this compound might be different. Chemically, it can be considered a nonhalogenated double-ester type glucocorticoid. More recently, further substances of this type have been synthesized and offered to the clinician. These compounds are not derived from prednisolone but from hydrocortisone. Reflecting their chemical structures they have been named hydrocortisone aceponate and hydrocortisone buteprate. Nevertheless, up to the present, some students of the field still believe
5 that topical glucocorticoids only differ in potency. A comprehensive monograph on the broad field of'topical corticosteroids' in general was pubhshed recently [Maibach HI, Surber C (eds): Topical Corticosteroids. Basel, Karger, 1992]; the present volume focuses on its subject in a more limited sense. Thus it can be concise; this makes the editors hope that it will be read by many dermatologists - not only those in research but also those in clinical practice. This might spread information on a new approach which may offer the possibility of decreased adverse effects. Munich/San Francisco, Calif. Hans C. Korting, MD Howard I. Maibach, MD Preface VIII
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